Trend, Predictors and Outcomes of Combined Mitral Valve Replacement and Coronary Artery Bypass Graft in Patients with Concomitant Mitral Valve and Coronary Artery Disease; A National Inpatient Sample Database Analysis

Combined mitral valve replacement (MVR) and coronary artery bypass graft (CABG) procedures have been the norm for patients with concomitant mitral valve disease (MVD) and coronary artery disease (CAD) with no large-scale data on their safety and efficacy. Methods The National Inpatient Sample (NIS) database (2002-2018) was queried to identify patients undergoing MVR and CABG. The major adverse cardiovascular events (MACE) and its components were compared using a propensity score-matched (PSM) analysis to calculate adjusted odds ratios (OR). Results A crude population of 6,145,694 (CABG-only 3,971,045, MVR-only 1,933,459, MVR+CABG 241,190), while a subset of matched cohort 724,237 (CABG-only 241,436, MVR-only 241,611 vs. MVR+CABG 241,190) was included in the PSM analysis. The combined MVR+CABG procedure had significantly higher adjusted odds of MACE (OR 1.13, 95% CI 1.11-1.14 and OR 1.96, 95% CI 1.93-1.99) and in-hospital mortality (OR 1.29, 95% CI 1.27-1.31 and OR 2.1, 95% CI 2.05-2.14) compared with CABG and MVR-alone, respectively. Similarly, the risk of post-procedure bleeding, major bleeding, acute kidney injury, cardiogenic shock, sepsis, need for intra-aortic balloon pump (IABP), mean length of stay (LOS) and total charges per hospitalization were significantly higher for patients undergoing the combined procedure. These findings remained consistent on yearly trend analysis favoring the isolated CABG and MVR groups. Conclusion Combined procedure (MVR+CABG) in patients with MVD and CAD appears to be associated with worse in-hospital outcomes, increased mortality and higher resource utilization compared with isolated CABG and MVR procedures. Randomized controlled trials are needed to determine the relative safety of these procedures in the full spectrum of baseline valvular and angiographic characteristics.

Resources for Cardiovascular Healthcare associated with 30-day Mortality in Acute Myocardial Infarction with Cardiogenic Shock

Background Although primary percutaneous coronary intervention (PCI) and mechanical circulatory support (MCS), such as extracorporeal membrane oxygenation (ECMO) or intra-aortic balloon pumping (IABP), have been widely used for acute myocardial infarction patients with cardiogenic shock (AMICS), their in-hospital mortality remains high. This study aimed to investigate the association of cardiovascular healthcare resources with 30-day mortality in AMICS. Methods This was an observational study using a Japanese nationwide administrative data (JROAD-DPC) of 260,543 AMI patients between April 2012 and March 2018. Of these, 45,836 AMICS patients were divided into three categories based on MCS use: with MCS (ECMO with/without IABP), IABP only, or without MCS. Certified hospital density and number of board-certified cardiologists were used as a metric of cardiovascular care supply. We estimated the association of MCS use, cardiovascular care supply, and 30-day mortality. Results The 30-day mortality was 71.2% for the MCS, 23.9% for IABP only, and 37.8% for the group without MCS. The propensity score-matched and inverse probability-weighted Cox frailty models showed that primary PCI was associated with a low risk for mortality. Higher hospital density and larger number of cardiologists in the responsible hospitals were associated with a lower risk for mortality. Conclusions Although the 30-day mortality remained extremely high in AMICS, indication of primary PCI and improvement in providing cardiovascular healthcare resources associated with the short-term prognosis of AMICS.

Sacubitril/valsartan reduces indications for arrhythmic primary prevention in heart failure with reduced ejection fraction: insights from DISCOVER-ARNI, a multicenter Italian register

Background This sub-study deriving from a multicenter Italian register (DISCOVER-ARNI) investigated whether sacubitril/valsartan in adjunction of optimal medical therapy(OMT) could reduce the rate of implantable cardioverter-defibrillator(ICD) indications for primary prevention in heart failure with reduced ejection fraction(HFrEF) according to European guidelines indications, and its potential predictors. Methods In this observational study, consecutive patients with HFrEF eligible for sacubitril/valsartan from 13 Italian centers were included. Lack of follow-up or speckle tracking data represented exclusion criteria. Demographic, clinical, biochemical and echocardiographic data were collected at baseline and after 6 months from sacubitril/valsartan initiation. Results Of 351 patients, 225(64%) were ICD carriers and 126(36%) were not ICD carriers (of whom 13 had not indication) at baseline. After 6 months of sacubitril/valsartan, among 113 non-ICD carriers despite having baseline left ventricular (LV)EF≤35% and New York Heart Asscociation(NYHA) class=II-III, 69(60%) did not show ICD indications; 44(40%) still fulfilled ICD criteria. Age, atrial fibrillation, mitral regurgitation>moderate, left atrial volume index(LAVi), and LV global longitudinal strain(GLS) significantly varied between the groups. With ROC curves, age≥75 years, LAVi≥42ml/m2 and LV GLS≥-8.3% were associated with ICD indications persistence (AUC=0.65,=0.68,=0.68 respectively). With univariate and multivariate analysis, only LV GLS emerged as significant predictor of ICD indications at follow-up in different predictive models. Conclusions Sacubitril/valsartan may provide early improvement of NYHA class and LVEF, reducing the possible number of implanted ICD for primary prevention in HFrEF. Baseline reduced LV GLS was a strong marker of ICD indication despite OMT. Early therapy with sacubitril/valsartan may save infective/hemorrhagic risks and unnecessary costs deriving from ICDs.

Intersecting single-cell transcriptomics and genome-wide association studies identifies crucial cell populations and candidate genes for atherosclerosis

Aim GWASs have discovered hundreds of common genetic variants for atherosclerotic disease and cardiovascular risk factors. The translation of susceptibility loci into biological mechanisms and targets for drug discovery remains challenging. Intersecting genetic and gene expression data has led to the identification of candidate genes. However, previously studied tissues are often non-diseased and heterogeneous in cell composition, hindering accurate candidate prioritization. Therefore, we analyzed single-cell transcriptomics from atherosclerotic plaques for cell-type-specific expression to identify atherosclerosis-associated candidate gene-cell pairs. Methods and Results We applied gene-based analyses using GWAS summary statistics from 46 atherosclerotic and cardiovascular disease, risk factors, and other traits. We then intersected these candidates with scRNA-seq data to identify genes specific for individual cell (sub)populations in atherosclerotic plaques. The coronary artery disease loci demonstrated a prominent signal in plaque smooth muscle cells (SKI, KANK2, SORT1) p-adj. = 0.0012, and endothelial cells (SLC44A1, ATP2B1) p-adj. = 0.0011. Finally, we used liver-derived scRNA-seq data and showed hepatocyte-specific enrichment of genes involved in serum lipid levels. Conclusion We discovered novel and known gene-cell pairs pointing to new biological mechanisms of atherosclerotic disease. We highlight that loci associated with coronary artery disease reveal prominent association levels in mainly plaque smooth muscle cell and endothelial cell populations. We present an intuitive single-cell transcriptomics-driven workflow rooted in human large-scale genetic studies to identify putative candidate genes and affected cells associated with cardiovascular traits. Collectively, our workflow allows for the identification of cell-specific targets relevant for atherosclerosis and can be universally applied to other complex genetic diseases and traits. Translational perspective GWAS identified a large number of genomic loci associated with atherosclerotic disease. The translation of these results into drug development and faster diagnostics remains challenging. With our approach, we cross-reference the GWAS findings for atherosclerotic disease with scRNA-seq data of disease-relevant tissue and bring the GWAS findings closer to the functional and mechanistic studies.

Social relationships and the risk of incident heart failure: Results from a prospective population-based study of older men

Background Limited social relationships, particularly in older adults, has been implicated as a risk factor for cardiovascular disease. However, little is known about the associations between poor social relationships and heart failure incidence. Methods Prospective study of socially representative men aged 60-79 years drawn from general practices in 24 British towns and followed up for a maximum of 18 years. 3698 participants with no previous diagnosis of heart failure were included. Information on social relationships was based on a combination of marital status, living circumstances, and social contacts with friends and family. These provided information on contact frequency, contact satisfaction, and a social relationship score (low to high) combining frequency and satisfaction with contact. Heart failure included both incident non-fatal heart failure and death from heart failure. Results Among 3698 participants, 330 developed heart failure. Men with low compared to high frequency of contact with family and friends had an increased risk of incident heart failure (hazard ratio (HR) 1.59, 95%CI 1.15-2.18); this remained statistically significant after adjustment for social class, behavioural and biological risk factors. Low compared to high scores for satisfaction with contacts was associated with increased risk of heart failure (adjusted HR = 1.54; 95%CI 1.14-2.07). Lower social relationship scores (combining frequency and satisfaction with contact) were associated with greater risk of incident heart failure (adjusted HR = 1.38, 95%CI 1.02-1.87). Marital status and living alone were not significantly associated with heart failure. Conclusion Weaker social relationships appear to increase the risk of developing heart failure in older age. Further research is needed to investigate pathways underlying these associations and to test whether interventions to strengthen social relationships can reduce the risk of heart failure.

Is the contemporary care of the older persons with acute coronary syndrome evidence-based?

Globally, ischaemic heart disease is the leading cause of death, with a higher mortality burden amongst older adults. Although advancing age is associated with a higher risk of adverse outcomes following acute coronary syndromes (ACS), older patients are less likely to receive evidence-based medications and coronary angiography. Guideline recommendations for managing ACS are often based on studies that exclude older patients, and more contemporary trials have been underpowered and produced inconsistent findings. There is also limited evidence for how frailty and comorbidity should influence management decisions. This review focuses on the current evidence base for the medical and percutaneous management of ACS in older patients and highlights the distinct need to enrol older patients with ACS into well-powered, large-scale randomised trials.

Association of Coronary artery Calcification and Thoracic Aortic Calcification with incident peripheral arterial disease in the Multi-Ethnic Study of Atherosclerosis (MESA)

Aim The association of subclinical atherosclerotic disease in the coronary arteries and thoracic aorta with incident peripheral arterial disease (PAD) is unknown. We investigated the association between coronary artery calcium score (CACs) and thoracic aortic calcium score (TACs) with incident clinical and subclinical PAD. Methods and results The Multi-Ethnic Study of Atherosclerosis (MESA) recruited 6,814 men and women aged 45 to 84 from four ethnic groups who were free of clinical cardiovascular disease at enrollment. CACs and TACs were measured from computed tomography scans. Participants with a baseline ABI≤0.90 or > 1.4 were excluded. Abnormal ABI was defined as ABI≤ 0.9 or > 1.4 at follow up exam. Multivariable logistic regression and Cox proportional hazards models were used to test the associations between baseline CACs and TACs with incident abnormal ABI and clinical PAD respectively. A total of 6,409 participants (female: 52.8%) with a mean age of 61 years were analyzed. Over a median follow up of 16.7 years, 91 participants developed clinical PAD. In multivariable analysis, each unit increase in log (CACS+1) and log (TACs+1) were associated with 23% and 13% (P < 0.01for both) higher risk of incident clinical PAD, respectively. In 5,725 (female:52.6%) participants with an available follow up ABI over median 9.2 years, each 1-unit increase in log (CACs+1) and log (TACs+1) were independently associated with 1.15-fold and 1.07-fold (P < 0.01for both) higher odds of incident abnormal ABI respectively. Conclusions Higher baseline CACs and TACs predict abnormal ABI and clinical PAD independent of traditional cardiovascular risk factor and baseline ABI.

HIV Infection and Risks of Morbidity and Death in Adults with Incident Heart Failure

Aims Human immunodeficiency virus (HIV) increases the risk of heart failure (HF), but whether it influences morbidity and mortality remains unclear. Methods and Results We investigated the risks of hospitalization for HF, HF-related emergency department (ED) visits, and all-cause death in an observational cohort of incident HF patients with and without HIV using data from three large U.S. integrated healthcare delivery systems. We estimated incidence rates and adjusted hazard ratios by HIV status at the time of HF diagnosis for subsequent outcomes. We identified 448 persons living with HIV (PLWH) and 3,429 without HIV who developed HF from a frequency-matched source cohort of 38,868 PLWH and 386,586 without HIV. Mean age was 59.5±11.3 years with 9.8% women and 31.8% Black, 13.1% Hispanic, and 2.2% Asian/Pacific Islander. Compared with persons without HIV, PLWH had similar adjusted rates of HF hospitalization (adjusted hazard ratio [aHR] 1.01 95% confidence interval [CI]:0.81-1.26) and of HF-related ED visits (aHR 1.22 [95%CI:0.99-1.50]), but higher adjusted rates of all-cause death (aHR 1.31 [95%CI:1.08-1.58]). Adjusted rates of HF-related morbidity and all-cause death were directionally consistent across a wide range of CD4 counts but most pronounced in the subset with a baseline CD4 count <200 or 200-499 cells/μl. Conclusions In a large, diverse cohort of adults with incident HF receiving care within an integrated healthcare delivery systems, PLWH were at an independently higher risk of all-cause death but not HF hospitalizations or HF-related ED visits. Future studies investigating modifiable HIV-specific risk factors may facilitate more personalized care to optimize outcomes for PLWH and HF.

Screening for subclinical rheumatic heart disease: Addressing borderline disease in a real-world setting

Introduction The World Heart Federation (WHF) criteria identify a large borderline rheumatic heart disease (RHD) category that has hampered the implementation of population-based screening. Inter-scallop separations (ISS) of the posterior mitral valve leaflet (PMVL), a recently described normal variant of the mitral valve, appears to be an important cause of mild mitral regurgitation (MR) leading to misclassification of cases as WHF ‘borderline RHD’. This study aims to report the findings of the Echo in Africa project (EIA), a large-scale RHD screening project in South Africa and determine what proportion of borderline cases would be re-classified as normal if there were a systematic identification of ISS-related MR. Methods A prospective cross-sectional study of underserved secondary schools in the Western Cape was conducted. Participants underwent a screening study with a handheld (HH) ultrasound device. Children with an abnormal HH study were re-evaluated with a portable laptop echocardiography machine. A mechanistic evaluation was applied in cases with isolated WHF ‘pathological’ MR (WHF ‘borderline RHD’). Results 5255 participants (mean age 15± years) were screened. 3439 (65.8%) were female. 49 cases of WHF ‘definite RHD’ (9.1 cases/1000 [95% CI, 6.8-12.1 cases/1000]) and 104 cases of WHF ‘borderline RHD’ (19.5 cases/1000[95% CI,16.0-23.7 cases/1000]) were identified. ISS-related MR was the underlying mechanism of MR in 48/68 cases classified as WHF ‘borderline RHD’ with isolated WHF ‘pathological’ MR (70.5%). Conclusion In a real-world, large-scale screening project, the adoption of a mechanistic evaluation based on the systematic identification of ISS-related MR markedly reduced the number of WHF ‘screen-positive’ cases misclassified as WHF ‘borderline RHD’. Implementing strategies that reduce this misclassification could reduce the cost- and labour-burden on large scale RHD screening programs.

High-intensity Statin Treatment Is Associated with Reduced Plaque Structural Stress and Remodelling of Artery Geometry and Plaque Architecture

Aims Plaque structural stress (PSS) is a major cause of atherosclerotic plaque rupture and major adverse cardiovascular events (MACE). We examined the predictors of changes in peak and mean PSS (ΔPSSpeak, ΔPSSmean) in three studies of patients receiving either standard medical or high-intensity statin (HIS) treatment. Methods and results We examined changes in PSS, plaque size and composition between 7,348 co-registered baseline and follow-up virtual-histology intravascular ultrasound images in patients receiving standard medical treatment (controls, n = 18) or HIS (atorvastatin 80mg, n = 20, or rosuvastatin 40mg, n = 22). The relationship between changes in PSSpeak and plaque burden (PB) differed significantly between HIS and control groups (p < 0.001). Notably, PSSpeak increased significantly in control lesions with PB > 60% (p = 0.04), but not with HIS treatment. However, ΔPSSpeak correlated poorly with changes in lumen and plaque area or PB, plaque composition or lipid lowering. In contrast, ΔPSSpeak correlated significantly with changes in lumen curvature, irregularity and roughness (p < 0.05), all of which were reduced in HIS patients. ΔPSSmean correlated with changes in lumen area, PA, PB, and circumferential calcification, and was unchanged with either treatment. Conclusion Our observational study shows that PSSpeak changes over time were associated with baseline disease severity and treatment. The PSSpeak increase seen in advanced lesions with standard treatment was associated with remodelling artery geometry and plaque architecture, but this was not seen after HIS treatment. Smoothing plaques by reducing plaque/lumen roughness, irregularity and curvature represent a novel mechanism whereby high-intensity statins may reduce PSS, and thus may protect against plaque rupture and MACE.